Dataset Information

Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants.

ABSTRACT: Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary. SIGNIFICANCE: Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.

SUBMITTER: Wang SC

PROVIDER: S-EPMC7489496 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline <i>CDH1</i> Variants.

Wang Sam C SC Yeu Yunku Y Hammer Suntrea T G STG Xiao Shu S Zhu Min M Hong Changjin C Clemenceau Jean R JR Yoon Lynn Y LY Nassour Ibrahim I Shen Jeanne J Agarwal Deepak D Reznik Scott I SI Mansour John C JC Yopp Adam C AC Zhu Hao H Hwang Tae Hyun TH Porembka Matthew R MR

Cancer research 20200408 11

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducte ...[more]

PMID: 32269045

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Project description:In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I ?2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy.

Project description:PurposeHispanic/Latino adults on the Texas-Mexico border have high rates of chronic disease. Neighborhoods can influence health, though there is a limited research on neighborhood environment and health in Hispanics/Latinos. The purpose of this study was to assess the relation of neighborhood environment with health variables in Hispanic/Latino adults, including physical activity [PA], depression, anxiety, and lab-assessed conditions (type 2 diabetes, metabolic syndrome, and chronic inflammation).MethodsParticipants were randomly-selected from a Hispanic/Latino cohort on the Texas-Mexico border. Neighborhood environment, self-reported PA, anxiety, and depression were assessed through questionnaires. Laboratory values determined Type 2 diabetes, metabolic syndrome, and C-reactive protein (CRP). We conducted multivariable linear and logistic regression analyses to assess the associations of neighborhood environment and health variables, controlling for covariates.ResultsParticipants (n = 495) were mostly females, without insurance. After controlling for covariates, crime (Adjusted Odds Ratio [AOR] = 1.59 (95%CI 1.06-2.38), no streetlights (AOR = 1.65, 95%CI 1.06-2.57), and traffic (AOR = 1.74, 95%CI 1.16-2.62) were all significantly associated with anxiety. Only traffic was significantly associated with depression (AOR = 1.61, 95%CI1.05-2.47). A lack of nearby shops (AOR = 0.57, 95%CI 0.38-0.84) and no one out doing PA (AOR = 0.53, 95% CI 0.34-0.83) were both significantly associated with lower odds of meeting PA guidelines. A lack of nearby shops was associated with a 26% increase in the CRP value (β = 0.26, 95%CI 0.04-0.47).DiscussionSeveral neighborhood environment variables were significantly associated with mental health, PA and CRP, though estimates were small. The neighborhood environment is a meaningful contextual variable to consider for health-related interventions in Hispanic/Latino adults, though more study is needed regarding the magnitude of the estimates.Trial registrationNCT01168765.

Dataset Information

Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline CDH1 Variants.

Publications

Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of Germline <i>CDH1</i> Variants.

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